Improved Methodology for the Preparation of Chiral Amines

attempts were directed for the asymmetric reductive amination of ketones under transfer
hydrogenation conditions but with limited success compared to ketone reduction.
Nevertheless, some useful recent breakthroughs have been achieved. [54] A remarkably
effective asymmetric version was reported by Kadyrov, Riermeier and Börner. [55] They
reported the use of several ruthenium and rhodium catalysts for the conversion of
acetophenone derivatives to the enantiomerically enriched amines (Scheme 3.17 ). According
to their strategy different aryl-alkyl ketones can be utilized as substrates producing the
primary amines in high yields (74-92%) and enantioselectivity (89-95%) in a one step
reaction. HCO 2 NH 4 was used as the hydride source with NH 3 as the nitrogen source and
different BINAP ligands were tested showing the best catalyst was [Ru-(R)-(TolBINAP)Cl 2 ].
In the reaction along with the primary amine a formyl derivative (RHNC(O)H) is produced
and in order to improve the yield the crude product is treated with HCl (EtOH/H 2 O) at reflux
to obtain the desired amine in a good to excellent yield. Despite these encouraging results the
application of this method is limited to the aromatic substrates in which other substrates as 1-
indanone (6% yield, no reported ee, chiral Ru catalyst) and aliphatic ketones, e.g. 2-octanone
(44% yield, 24% ee, using chiral Ru catalyst) showed unsatisfactory results (scheme 3.16).
R'
O
R
(i)1 mol% [Ru-(R)-TolBINAP(Cl) 2 ]
NH 4 HCO 2 ,NH 3 /MeOH (15-20%), 85 o C
(ii) 6N HCl, reflux, 1h
R'
H NH 2
R
Aryl group R Yield and ee
Ph Me 92, 95% ee R
Ph Et 89, 95% ee R
3-MeC 6 H 4 Me 74, 89% ee R
4-MeC 6 H 4 Me 93, 93% ee R
4-ClC 6 H 4 Me 93, 92% ee R
4-(NO 2 )C 6 H 4 Me 92, 95% ee R
Scheme 3.16. Transfer Hydrogenation of Acetophenone Derivatives.
3.4.5. Organocatalytic Asymmetric Reductive Amination:
The use of organocatalysts was slowly introduced to organic chemistry over the last two
decades. There were earlier trials of using organic compounds to catalyze organic reactions
but the low yields and stereoselectivities were discouraging. Recent advances in
spectroscopic and asymmetric techniques have opened the door for the synthesis of a big
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